Relative Influence of Scaffold Design/Material Parameters On Bone Regeneration

描述(申请人提供)：骨支架应提供足够的承重和促进组织再生。然而，目前，很少有严格的比较信息可以告诉人们，具有特定建筑设计的特定材料将提供足够的载荷，并提供最佳的骨再生。作为起点，我们将承重与有效的弹性和强度联系起来，并以渗透性材料作为设计变量来促进组织再生。那么根本的问题就变成了“支架能否在设计时保持最小的承载特性，同时最大化渗透性？相对于材料的骨传导性，渗透性对骨再生有多重要？”我们推测骨组织工程支架应该由最具渗透性的骨传导材料构建而成，以促进骨再生。此外，支架的设计应使其在0时间的力学性能达到50兆帕的模数和2兆帕的抗压强度，在人体松质骨范围内。与这一假设相关，我们试图回答以下问题：1)支架能否设计成满足最低50/2 Mpa的刚度/强度标准，这些力学性能的退化如何取决于渗透性和材料？2)渗透性在骨再生中起重要作用还是材料是压倒性的因素？我们将通过三个具体目标来回答这些基本的支架设计问题：具体目标1：通过计算设计和制作具有最大和次最大渗透率的HA/TCP、PLLA和PCL单孔率为60%的支架结构。具体目标2：确定所设计的支架在0的弹性模量值和极限强度满足最小人体松质骨值。确定设计/材料如何影响机械特性的退化。具体目标3：通过转导BMP-7的人成纤维细胞，确定设计的渗透性和材料对8周、16周小鼠模型骨再生的影响。这项研究将为骨组织工程师提供关于支架渗透性和材料骨组织支架设计的相对重要性的关键信息，这将对骨组织工程的临床应用至关重要。

DESCRIPTION (provided by applicant): Bone scaffolds should provide adequate load bearing and enhance tissue regeneration. However, at present, there is little rigorous comparative information that will tell one that a given material with a given architecture design will provide adequate load bearing and give the best bone regeneration. As a starting point, we associate load bearing with effective elasticity and strength, and enhanced tissue regeneration with permeability material as design variables. Then the fundamental question becomes "can scaffolds be designed to maintain minimum loading bearing characteristics while maximizing permeability and how important is permeability for bone regeneration relative to material osteoconductivity?" We hypothesize that Bone tissue engineering scaffolds should be fabricated from the most osteoconductive material with maximal permeability to enhance bone regeneration. Furthermore, the scaffold design should be such that the mechanical properties at time 0 can achieve a modulus of 50 MPa and compressive strength of 2 MPa, within the range of human trabecular bone. Related to this hypothesis, we seek to answer the questions: 1) can scaffolds be designed to meet the minimum 50/2 MPa stiffness/strength criteria and how does degradation of these mechanical properties depend on permeability and material?, and 2) does permeability play a significant role in bone regeneration or is material an overwhelming factor? We will answer these fundamental scaffold design questions through three specific aims: Specific Aim 1: Computationally design and fabricate scaffolds architectures from HA/TCP, PLLA, and PCL at a single porosity of 60% with maximal and sub-maximal permeability Specific Aim 2: Determine elastic modulus and ultimate strength of designed scaffolds at 0 meet minimum human trabecular bone values. Determine how design/material influence degradation of mechanical properties. Specific Aim 3: Determine the influence of designed permeability and material on bone regeneration in a mouse model at 8, and 16 weeks by delivering BMP-7 transduced human fibroblasts. This study will give bone tissue engineers critical information as to as to the relative importance of scaffold permeability and material bone tissue scaffold design, which will be crucial for clinical bone tissue engineering applications.